Solidification of volatile D-Limonene by cyclodextrin metal-organic framework for pulmonary delivery via dry powder inhalers: In vitro and in vivo evaluation

[Display omitted] D-Limonene (D-Lim), a volatile oil extracted from citrus fruits, has therapeutic effects on lung inflammation and cancer, whilst the deep delivery of D-Lim was challenging due to its physical instability for a long period of time. To prevent the volatilization of D-Lim and achieve...

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Bibliographic Details
Published in:International journal of pharmaceutics 2021-09, Vol.606, p.120825-120825, Article 120825
Main Authors: Zhou, Yong, Zhang, Meijuan, Wang, Caifen, Ren, Xiaohong, Guo, Tao, Cao, Zeying, Zhang, Jiwen, Sun, Lixin, Wu, Li
Format: Article
Language:English
Subjects:
Aerosolization
Bioavailability
D-Limonene
Dry powder inhaler
Solidification
γ-cyclodextrin metal-organic framework
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Summary:[Display omitted] D-Limonene (D-Lim), a volatile oil extracted from citrus fruits, has therapeutic effects on lung inflammation and cancer, whilst the deep delivery of D-Lim was challenging due to its physical instability for a long period of time. To prevent the volatilization of D-Lim and achieve efficient pulmonary delivery, herein, D-Lim was loaded into biodegradable γ-cyclodextrin metal-organic framework (γ-CD-MOF) with optimal loading efficiency achieving 13.79 ± 0.01% (molar ratio of D-Lim and γ-CD-MOF was 1.6:1), which possessed cubic shape with controllable particle size (1–5 μm). The experimental results indicated that γ-CD-MOF could improve the stability of D-Lim. A series of characterizations and molecular docking were used to reveal the interaction between D-Lim and γ-CD-MOF. The solidification of D-Lim by γ-CD-MOF played a crucial role in the exploitation of its inhalable dosage form, dry powder inhaler (DPI). Specifically, the aerosolization of D-Lim@γ-CD-MOF for inhalation was satisfactory with a fine particle fraction (FPF) of 33.12 ± 1.50% at 65 L/min of flow rate. Furthermore, in vivo study had shown a 2.23-fold increase in bioavailability of D-Lim solidified by γ-CD-MOF for inhalation compared to D-Lim for oral administration. Therefore, it is considered that γ-CD-MOF could be an excellent carrier for pulmonary drug delivery to realize solidification and lung therapeutic effects of volatile oils.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2021.120825